Field effect in cancer-an update.

The concept "field effect in cancer" originated in 1953 from the histopathological observations of Slaughter and colleagues [1] regarding the occurrence of multiple primary oral squamous cell carcinomas and their local recurrences. The development of modern molecular technologies has extended the field effect concept by exploring the molecular abnormalities in tissues that appear histologically normal. To date, such field effect biomarkers have been reported in several sites and organs, eg, head and neck, colon and rectum, prostate, breast, lung, esophagus, stomach, and skin. Two popular hypotheses have been proposed. One hypothesis implicates genetic alterations that occur in a stepwise fashion (initiation, promotion, and progression); a clone gains growth advantage and acquires more genetic alterations, which eventually result in cancer. A second hypothesis focuses on epigenetic alterations, which include hypermethylation of the DNA promoter of certain tumor suppressor genes, leading to down-regulation of these genes. In this update, we discuss in detail the evidence that supports these two hypotheses. In addition, we attempt to provide a comprehensive overview of the field effect in carcinogenesis and its possible mechanisms in various organs. Moreover, we discuss the potential utilization of field effect biomarkers in cancer prevention, surgical considerations, and clinical prognosis.